Lecture #10: Antigens and Antigen Processing

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Questions and Answers

What distinguishes an immunogen from an antigen?

An immunogen does not interact with immune system receptors.

Only an immunogen can induce a specific immune response. (correct)

All antigens are immunogens in terms of functionality.

Antigens are always foreign substances to the body.

Which of the following is NOT considered an antigen?

A viral protein

Normal host cell molecules

Animal dander

Antibodies produced after an immunogen exposure (correct)

Which statement about antigens is accurate?

All antigens can generate antibodies.

Antigens can originate from neoplastic host cells. (correct)

Antigens must be foreign to trigger an immune response.

Only microbial proteins act as antigens.

Which of the following types of antigens are associated with Streptococcus pneumoniae?

Polysaccharide antigens Signup and view all the answers

What is a defining feature of an antibody?

It is a protein synthesized in response to an antigen. Signup and view all the answers

What defines an allergen?

A substance that causes a detrimental allergic reaction Signup and view all the answers

Which of the following describes a tolerogen?

An antigen that leads to immune non-responsiveness due to its molecular form Signup and view all the answers

What is true about tumor-specific antigens (TSAs)?

They are typically a result of tumor-specific mutations Signup and view all the answers

Which statement best defines tumor-associated antigens (TAAs)?

They are more common than tumor-specific antigens Signup and view all the answers

What is an epitope?

The portion of an antigen that a TCR binds to Signup and view all the answers

What type of antigens are considered good immunogens?

Pure proteins and glycoproteins Signup and view all the answers

Which component is essential for a hapten to induce an immune response?

It must be coupled to a larger carrier molecule Signup and view all the answers

Which of the following is not a characteristic of tumor-specific antigens (TSAs)?

They lead to immune system tolerance Signup and view all the answers

What distinguishes immunogens from haptens?

Immunogens can elicit an immune response, while haptens cannot. Signup and view all the answers

Which of the following is true about T-dependent antigens?

They typically have multiple epitopes. Signup and view all the answers

What is the primary role of the MHC Class I molecules?

Presenting endogenous antigens to CD8+ T cells. Signup and view all the answers

Which of the following molecules play a key role in peptide loading onto MHC Class II?

Invariant chain/CLIP Signup and view all the answers

What is the significance of polymorphism in MHC molecules?

It enhances the ability to recognize a wider variety of antigens. Signup and view all the answers

How are exogenous antigens processed for MHC Class II presentation?

After being phagocytosed and processed within endosomes. Signup and view all the answers

Which component is essential for cross-presentation to CD8+ T cells?

HLA-DM Signup and view all the answers

What characteristic is common to T-independent antigens?

They are typically polysaccharides or lipids. Signup and view all the answers

What occurs when the pAPC recognizes foreign proteins as viral?

It presents the viral proteins via MHC I. Signup and view all the answers

What type of T cells do CD8+ cells differentiate into after activation?

Cytotoxic T lymphocytes (CTLs) Signup and view all the answers

What is the primary function of CD4+ T cells in the immune response?

To assist other immune cells by releasing cytokines Signup and view all the answers

Which of the following best describes cross-presentation?

Presentation of exogenous antigens on MHC I molecules Signup and view all the answers

How do class I and class II MHC molecules differ in terms of the antigens they present?

Class I presents endogenous antigens, class II presents exogenous antigens. Signup and view all the answers

Which cell types primarily recognize antigens presented by MHC I and MHC II molecules respectively?

CD8+ T cells and CD4+ T cells Signup and view all the answers

What is the role of the proteosomal processing mechanism in the context of MHC I presentation?

It degrades endogenous proteins for presentation. Signup and view all the answers

What typically happens if the classical pathway for exogenous antigen processing is followed?

Only a CD4+ helper response occurs. Signup and view all the answers

What is identified as the major determinant of graft acceptance or rejection?

HLA genotype Signup and view all the answers

Which class of MHC molecules does HLA-A belong to?

Class I Signup and view all the answers

What percentage chance do siblings have of inheriting identical sets of HLA alleles?

25% Signup and view all the answers

What term describes the set of MHC genes present on each chromosome?

HLA haplotype Signup and view all the answers

What does the polymorphism of the MHC molecules affect?

The recognition of peptide antigens Signup and view all the answers

How many alleles are estimated to exist for MHC (HLA) in humans?

More than 14,000 Signup and view all the answers

What is the co-dominant expression of MHC genes?

Both parental alleles are expressed equally Signup and view all the answers

What is the primary function of histocompatibility molecules?

Displaying peptide antigens to T cells Signup and view all the answers

Which class of HLA molecules includes HLA-DR?

Class II Signup and view all the answers

What is the significance of the term 'histo' in histocompatibility?

It relates to tissue compatibility Signup and view all the answers

Which type of T cells primarily recognize Class II MHC molecules?

CD4 T cells Signup and view all the answers

What is the primary source of peptides presented by Class I MHC molecules?

Cytosolic proteins Signup and view all the answers

How do hapten-specific B cells interact with helper T cells?

By binding to antigens via hapten determinants Signup and view all the answers

What must be true for an efficient response involving a hapten and its carrier protein?

Hapten and carrier must be physically linked Signup and view all the answers

In the context of T cell recognition, what are CD4 and CD8 T cells primarily binding to?

Nonpolymorphic regions of MHC Signup and view all the answers

What is the role of endogenous antigens during MHC molecule assembly?

They are presented by Class I MHC molecules Signup and view all the answers

Why is the binding of a hapten to a carrier protein important?

It allows B cells to recognize multiple epitopes Signup and view all the answers

Which mechanism allows APCs to present extracellular antigens to T cells?

Endocytosis of antigens and MHC assembly Signup and view all the answers

Study Notes

Antigens, Antigen Processing & Presentation

Lecture objectives include differentiating antigens, immunogens, epitopes, and haptens; recognizing different types of antigens and their immunogenicity; defining T-dependent and T-independent antigens; and describing MHC inheritance.
Contrast the cellular expression of MHC Class I and Class II molecules.
Identify the importance of MHC Class I and Class II gene polymorphism for antigen processing and transplantation.
Diagram and label a Class I and Class II MHC molecule, including polypeptide chains, beta 2 microglobulin, peptide binding groove, bound peptide, anchor residues/pockets, TCR binding sites, and CD4/CD8 binding sites.
Identify key steps in exogenous and endogenous antigen processing, including the role of TAP, proteasome, chaperones, invariant chain/CLIP, and HLA-DM.
Describe the cellular/molecular mechanism and significance of cross-presentation.
Antigens are substances that react with products of a specific immune response (antibody-generating agent) and can be microbial or otherwise foreign to the body.

What is it that our immune system recognizes?

Understanding the concepts of antigens, immunogens, epitopes, and haptens is necessary to grasp the immune system's recognition mechanisms.
It's necessary to differentiate between various types of antigens and their immunogenicity.

Antigens

Antigens can be neoplastic or normal host cells (e.g., cancerous or normal prostate cells).
Antigens can also be microbial proteins and carbohydrates (e.g., Streptococcus pneumoniae polysaccharides, viral proteins, and carrier proteins).
Antigens are also present in environmental factors—like pollen and animal dander.
Blood types (e.g., Antigen A, Antigen B) are also examples of antigens found in the human body.

Terms to Know: Antigens & Immunogens

Antigens react with the products of a specific immune response.
Immunogens induce a specific immune response.
Antibodies are proteins that are produced in response to an immunogen and react with antigens.
All immunogens are antigens, but not all antigens are immunogens.

An Antigen by Any Other Name...

Allergens cause detrimental allergic reactions.
Tolerogens induce immune non-responsiveness.
Tumor-specific antigens (TSAs) result from tumor-specific mutations.
Tumor-associated antigens (TAAs) are antigens on tumor cells and normal cells (more common than TSAs).

Terms to Know: Epitope

Epitopes, also called antigenic determinants, are portions of an antigen that combine with the products of a specific immune response.
B cell epitopes are specific portions of macromolecular antigens that are recognized by antibodies (Abs).
T cell epitopes are peptide portions that are recognized by T cell receptors (TCRs) when displayed bound to an MHC molecule.

Chemical Nature of Different Types of Antigens

Proteins (e.g., pure proteins, glycoproteins, lipoproteins) are usually very good immunogens.
Polysaccharides (e.g., pure polysaccharides, lipopolysaccharides) are good immunogens.
Nucleic acids are usually poorly immunogenic, but can become immunogenic when single-stranded or complexed with proteins.
Lipids are typically non-immunogenic, but some can be haptens.
Haptens are small low-molecular-weight compounds. They induce an immune response only when coupled to a larger carrier molecule (usually a protein).

Relative Immunogenicity of Various Antigens

The relative immunogenicity of different antigens differs based on their chemical nature, with proteins generally being more immunogenic than carbohydrates or lipids, and haptens only eliciting an immune response when coupled with a carrier.

Features of Biological Antigens Recognized

B cell epitopes can be macromolecules (proteins, polysaccharides, nucleic acids, lipids), small chemicals, and conformational or linear.
T cell epitopes can be proteins/polypeptides and linear or other relevant sequences to MHC.

Antigens Stimulate Adaptive Immune Responses

Antigens stimulate immune responses through humoral and cellular pathways.
Adaptive immune responses involve the production and secretion of antibodies (B cells), and the killing of infected cells (T cells)

How does the innate immune system stimulate adaptive responses?

Innate responses warn the adaptive system an effective response is needed.
Two signals are required for lymphocyte activation (signal 1: antigen recognition by lymphocytes, and signal 2: cytokines, microbial peptides, degradation products of innate responses).

Recognition by Lymphocytes

Lymphocytes recognize antigens via receptors (membrane-bound or soluble).
Lymphocytes use accessory molecules like MHC molecules to enhance antigen recognition.

Antigens can elicit a B cell response in two primary ways

T-dependent antigens require T cell help for immune responses (humoral-IgG, IgA, or IgE).
T-independent antigens don't require T cell help for immune responses (humoral- IgM mostly).

Antigen processing and presentation to T cells

Antigen-presenting cells (APCs) process and present antigen to T cells in two pathways (exogenous and endogenous).

How are MHC molecules inherited?

MHC molecules are inherited in a specific pattern with a high degree of polymorphism.

Discovery of the Human Major Histocompatibility Complex (MHC)

MHCs were discovered through studying individuals who had received multiple blood transfusions or kidney transplants and noted immune responses against the transplanted tissue.

Proteins encoded by MHC (HLA)

MHC proteins are referred to as HLA proteins in humans, and various genes govern various groups of MHC proteins.
These genes are closely linked on a chromosome.
There's a chance that siblings will inherit identical sets of HLA alleles.

Inheritance and Expression of MHC

Each haplotype contains loci encoding all Class I and II MHC molecules. Every person inherits one haplotype from each parent.
High polymorphism in MHC proteins.
Protein products of both parental alleles at a given locus are expressed equally.

Implication of Polymorphism

Polymorphism in MHC genes allows individuals to present and respond to different microbial peptides.

Implications of Polymorphism-2

MHC molecules determine compatibility of grafted tissue.
HLA alleles are the major determinant of graft acceptance or rejection.

What Does the MHC molecule look like?

Different MHC molecules display protein or other relevant polypeptide structures on their surfaces that bind and present antigen.

Which cells express which MHC?

All nucleated cells express MHC Class I molecules, whereas dendritic cells, macrophages, and B cells express MHC Class II molecules.

MHC Structure

MHC I structure is composed of an alpha chain and beta-2 microglobulin.
MHC II structure is composed of alpha and beta chains with the addition of a peptide binding groove.

Peptide Binding

MHC polymorphism is largely confined to the peptide-binding cleft.
Different MHC isoforms bind peptides selectively, not with antigen specificity.
Non-polymorphic areas allow for co-receptors to bind (e.g., CD4 to Class II receptors and CD8 to Class I receptors).

Features of Peptide Binding to MHC

Each MHC molecule displays only one peptide at a time, recognizing many peptides.

Features of Peptide Binding to MHC (Continued)

MHC molecules display peptides from different cellular compartments.
Stable surface expression of MHC requires a bound peptide and a slow off-rate.

Protein Antigens Capture by Antigen-Presenting Cells

Protein antigens are captured from various body sites (e.g., skin, gastrointestinal tract, respiratory tract) and transported to lymph nodes.

Capture, Transport and Presentation of Protein Antigens by Dendritic Cells

Dendritic cells are specialized cells that capture, transport, and present protein antigens to T cells for activation.

Summary: Features of Antigens Recognized by T Cells

Most T cells recognize peptides.
T cells recognize linear peptides, not conformational structures.
T cells recognize cell-associated, not soluble antigens.
Different CD4+ and CD8+ T cells recognize different protein pools (intracellular/extracellular).

Are Haptens Recognized by T Cells?

Haptens bind to carrier proteins and are recognized by B-helper T cells, however T cells do not directly recognize them on their own.

A Model for T Cell Recognition of Peptide-MHC Complex

TCR interacts with peptide bound to MHC molecules.
Polymorphic residues of MHC and anchor residues of the peptide contribute to the specificity of the interaction.

What are the steps in the MHC pathways of peptide degradation and presentation?

The pathways of exogenous and endogenous pathways differ, but the overall goal of presenting peptides for TCR-MHC binding is the same.

Overview of Antigen Processing and Presentation

Different pathways for processing antigens exist based on the localization of antigens.
Antigen localization in the cell will influence the nature of the immune response.
APCs transport antigens via endosomal vesicles or other processes to present to T cells.

Overview of Antigen Processing and presentation pathways

The processes of antigen uptake, processing, biosynthesis and assembly of MHC molecules, and peptide-MHC association are crucial steps leading to the antigen presentation that activate T-cells for appropriate response.

Class II MHC pathway: Processing of Internalized Protein Antigens

Explains the steps and molecules involved in internalizing exogenous proteins, processing by enzymes in endocytic vesicles, and presenting the digested peptides to the CD4+ helper T cells.

Processing of Intracellular/Cyosolic Protein

Describes the endogenous pathway of processing intracellular proteins, degrading proteins in the cytosol, and ultimately associating peptides produced with MHC class I.

Features of the Pathways of Antigen Processing

Shows the differences between the pathways for presenting different classes of endogenous/exogenous antigens. It emphasizes the roles of molecules like TAP, CLIP, and certain proteins.

Cross Presentation (aka Cross-priming)

Involves the uptake and display of exogenous antigens on MHC class I molecules. Enables CD8+ T cell responses to extracellular pathogens/virus infections in infected cells.
It discusses how MHC class II can bind to the processed antigen on some professional antigen presenting cells (APCs).

What happens when an infected cell is ingested 1 and 2?

Discusses why and how an infected cell is ingested by antigen presenting cells and how internalized antigens are processed to be presented to other immune cells.

What happens when an infected cell is ingested 3?

The antigen from the infected cell is processed and presented on both MHC Class I and Class II to activate T cells.

What Comes Next

The cellular and molecular steps necessary for activation CD4+ and CD8+ T cells following antigen recognition.

On Your Own Thought Questions

Consists of a set of questions requiring students to analyze, evaluate, and synthesize information on the topic.

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Description

Test your knowledge on the distinctions between immunogens, antigens, and antibodies. This quiz covers key concepts such as types of antigens, their characteristics, and the role they play in immune responses. Ideal for students and enthusiasts in the field of immunology.